tbuckley/cabot-search huggingface dataset:
FRONTIER: FAPi radioligand open-label, phase 1 study to evaluate safety, tolerability and dosimetry of [Lu-177]-PNT6555—A dose escalation study for treatment of patients with select solid tumors.
Authors: Lisa Bodei, Petr Kavan, Moishe Liberman, Neil Taunk, Ur Metser, Daniel Juneau, Eileen Mary O'Reilly, Junsheng Ma, Richard Cioci, Albiruni Ryan Abdul Razak
Journal: Journal of Clinical Oncology (2023)

TPS3161 Background: Fibroblast activation protein alpha (FAP) is a 170 kDa transmembrane glycoprotein expressed during development, active tissue remodeling, and cancer. Overexpression on cancer-associated fibroblasts in the tumor microenvironment, and on some cancer cells of mesenchymal origin, leads to the presence of FAP in &gt; 90% of epithelial tumors, making FAP a compelling anti-cancer target. PNT6555, a potent FAP-targeting compound with rapid clearance from normal tissues and prolonged tumor retention in preclinical models 1 , is a radioligand consisting of a DOTA chelator (1,4,7,10-tetraazacyclododecane-1,4,7,10- tetraacetic acid) and a FAP-targeting moiety (Bz-D-Ala-boroPro) connected via an aminomethyl linker. The corresponding gallium-68 and lutetium-177 chelates constitute the imaging and therapeutic theranostic pair of PNT6555 under evaluation in this phase I study. Methods: FRONTIER (NCT05432193) is a multicenter, open-label, multi-dose phase I study of PNT6555 in participants with pancreatic ductal adenocarcinoma, esophageal cancer, colorectal cancer, melanoma skin cancer, cholangiocarcinoma, or soft tissue sarcoma solid tumors with FAP over-expression. The primary aim is to evaluate the safety and tolerability of [Lu-177]-PNT6555 in order to determine a recommended phase II dose (RP2D). Dosimetry, pharmacokinetics, and tumor and immune responses will also be assessed for [Lu-177]-PNT6555, as well as safety, tolerability, and diagnostic performance of [Ga-68]-PNT6555 PET/CT. Key eligibility criteria include being refractory to prior treatment with no alternative available therapeutic options, having adequate organ function, and being FAP-positive on [Ga-68]-PNT6555 PET/CT scan, defined as ≥50% of lesions with an SUV max of ≥1.5x the liver SUV mean . [Ga-68]-PNT6555 will be dosed at 120 - 220 MBq (3.2 - 5.9 mCi), with PET/CT initiated 90 (±30) min later. FAP-positive participants will receive [Lu-177]-PNT6555 once every 6 weeks for up to 6 cycles. Starting at 4 GBq (108 mCi) ±10%, [Lu-177]-PNT6555 may be escalated by 4 GBq, with a maximum planned dose of 12 GBq. De-escalation by 2 GBq may also occur. Dose finding will be guided by the modified toxicity probability interval (mTPI-2) statistical design with a targeted toxicity rate of 30%. The planned total sample size is 30, with targets of 3-12 DLT evaluable patients per dose level. Cohort 1 has been completed without a DLT. Enrollment to cohort 2 began in January 2023. 1. Hallet R, et al. Pre-clinical characterization of the novel fibroblast activation protein (FAP) targeting ligand PNT6555 for the imaging and therapy of cancer. Presented at SNMMI Annual Meeting April 2022; Vancouver, BC, Canada. Clinical trial information: NCT05432193 .
Analysis of hospitalizations of patients with penile cancer: A national population-based study.
Authors: Philip Onyekaoso Kanemo, Ted Akhiwu, Ayobami Gbenga Olafimihan, Ehizogie Edigin, Anthonia Ijeli, Muhammad Bilal Ibrahim, Osaigbokan Aihie, Dan Ran Castillo, Muhammad Nauman Riaz
Journal: Journal of Clinical Oncology (2023)

e17033 Background: Penile cancer (PC) is a rare malignancy that is more common in developing countries. However, recent studies have shown rising incidence-based mortality in the United States (U.S). National population data is scarce on reasons for hospitalizations, epidemiology, and hospitalization outcomes of patients with PC. Methods: Data were abstracted from the National Inpatient Sample (NIS) 2020 Database. T≥his database is the largest collection of inpatient admission data in the U.S. It is a 20-percent stratified sample of all discharges from U.S. community hospitals, excluding rehabilitation and long-term acute care hospitals. The numbers in the databases are weighted to optimize national estimates. Hospitalizations for patients with PC were obtained by searching for hospitalizations that contained the International Classification of Diseases (ICD)-10 code “C60” as a principal or secondary diagnosis. The principal diagnosis is the main reason for the admission, while any other diagnosis other than the principal, are secondary diagnosis. The reason for hospitalization (or principal diagnosis) was recorded in descending order of frequency based on the ICD-10 code organ system category and specific principal diagnosis. The total number of PC discharges, baseline demographic characteristics, hospital length of stay (LOS), and total hospital charges were recorded. STATA 16 was used for analysis. Since NIS contains de-identified data, Institutional Review Board (IRB) review was waived. Results: There were 32 million discharges included in the 2020 NIS database. Of those, 2,785 hospitalizations were for patients aged ≥18 years, who had either a principal or secondary ICD 10 code for PC. Patients were predominantly white (65.9%), mean age of 66.5 years, inpatient mortality of 4.7%, mean LOS of 6.1 days, and mean total hospital charge of 71,447 U.S dollars. The 7 most common reasons for hospitalization by ICD 10 code categories were neoplasm and hematological (35.9%), nonspecific (17.3%), infections (12.6%), injury &amp; poisoning (7.1%), cardiovascular (6.4%), and Genito-urinary (4.3%). The 5 most common specific principal diagnoses for hospitalizations were malignant neoplasm of the penis (29.1%), admission for chemotherapy (12.7%), sepsis (2.7%), Malignant neoplasm of the glans penis (2.2%), secondary neoplasm of inguinal and lower limb nodes (1.8%). Conclusions: Hospitalized PC patients are mostly elderly white men. Infections, chemotherapy, and PC were the most common reasons for hospitalizations. Optimal management of underlying malignancy, prevention, and prompt treatment of infections in the outpatient is important in reducing hospitalizations of these patients.
Identifying the optimal therapeutics for patients with hormone receptor-positive, HER2-positive advanced breast cancer: A systematic review and network meta-analysis.
Authors: Yan Wang, Hangcheng Xu, Yiqun Han, Yun Wu, Qiang Sa, Binghe Xu, Jiayu Wang
Journal: Journal of Clinical Oncology (2023)

e13023 Background: Hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-positive breast cancer is a distinct subtype with different prognosis and response to treatment. HER2-targeted therapy is currently recommended for patients with HR+/HER2+ advanced breast cancer. However, there is debate over which drugs to add on the basis of HER2 blockade yields the optimal efficacy. Moreover, the research on replacing chemotherapy with endocrine therapy in the regimens are under way. This systematic review and network meta-analysis was conducted to find the optimal treatment for this subtype. Methods: Eligible randomized controlled trials (RCTs) comparing different interventions in metastatic HR+/HER2+ breast cancer were included by comprehensively searching PubMed, Embase, the Cochrane Library, ClinicalTrials.gov, and abstracts of oncology conferences before September 5 th , 2022. The outcomes of interest included progression free survival (PFS), overall survival (OS) and treatment-related adverse events (TRAEs). Pooled hazard ratios (HRs) or odds ratios (ORs) with credible intervals (CrIs) were calculated to estimate the predefined outcomes based on the data type. The optimal therapeutics were identified by utilizing the cumulative ranking curves (SUCRA). Results: In total, 23 pieces of literature of 20 RCTs were included. Regarding PFS, significant differences were detected between dual HER2 blockade plus endocrine therapy versus endocrine therapy alone (HR 0.45, 95% CrI 0.25-0.83; HR 0.47, 95% CrI 0.27-0.87), and trastuzumab, pertuzumab plus chemotherapy versus trastuzumab plus chemotherapy (HR 0.69, 95% CrI 0.47-0.96). The SUCRA values suggested the relatively better efficacy of dual HER2-targeted therapy plus endocrine therapy (86% to 91%) or chemotherapy (62% to 81%) in prolonging PFS and OS. The HER2 blockade-containing regimens showed similar safety profiles in eight documented TRAEs. Conclusions: Prominent status of dual-targeted therapy for patients with HR+/HER2+ metastatic breast cancer was revealed. Compared with chemotherapy-containing regimens, the endocrine therapy-containing regimens showed better efficacy and similar safety profile, which could be recommended in practice.
Safety and efficacy study of oral metronomic capecitabine in combination with pyrotinib for HER2-positive metastatic breast cancer: A phase II trial.
Authors: Qiao Li, Maiyue He, Jiaxuan Liu, Zijing Wang
Journal: Journal of Clinical Oncology (2023)

e13038 Background: A single-arm prospective phase II trial to was conducted evaluate the efficacy and safety of oral metronomic capecitabine combined with pyrotinib in human epidermal growth factor receptor 2-positive (HER2 positive) metastatic breast cancer (MBC) patients. Methods: HER2-positive patients received oral metronomic capecitabine 500 mg three times daily and pyrotinib 400 mg. The primary endpoint was progression-free survival (PFS). Other endpoints included objective response rate (ORR), clinical benefit rate (CBR), overall survival (OS), and safety. Results: 50 patients with HER2-positive MBC were enrolled, and one was excluded due to medication irregularities. The median PFS and OS were 11.9 months (95%CI 8.8-14.6) and 29.3 months (95%CI 24.4-34.8) respectively. ORR was 34.7%, and CBR was 81.6% with 2 CR (4.1%), 15 PR (30.6%) and 23 SD (46.9%). The mPFS in first- or second-line treatment was 12.2 months. The most frequent treatment-related adverse complications included hand-foot syndrome, diarrhea, vomiting and nausea. Grade 3 adverse events occurred in 15 (30.6%) patients and included hand-foot syndrome (12.2%), diarrhea (12.2%), vomiting (4.1%), and nausea (2.0%). Grade 4 adverse event of diarrhea (2.0%) was observed in one case. Conclusions: The combination of metronomic capecitabine and pyrotinib is a promising regimen with competitive efficacy and improved tolerability in HER2-positive metastatic breast cancer patients. Clinical trial information: NCT03923166 .
Engagement of Patients with Advanced Cancer (EPAC) randomized clinical trial: Long-term effects on survival and healthcare use.
Authors: Manali I. Patel, Madhuri Agrawal, Kris Kapphahn, Douglas W. Blayney, Steve Asch, M. Kate Bundorf, Arnold Milstein
Journal: Journal of Clinical Oncology (2023)

1513 Background: The Engagement of Patients with Advanced Cancer (EPAC) randomized Veterans with newly diagnosed stage 3 or 4 cancer or recurrent disease to usual care (control) or usual care with 6-month community health worker (CHW) support (intervention) to engage Veterans in end-of-life (EOL) goals and care preference discussions. At 6- and 15-months follow-up, the intervention tripled goals of care documentation (primary outcome), doubled hospice (secondary outcome), and reduced end-of-life (EOL) acute care use (secondary outcome). This post-hoc analysis after 10 years from study initiation evaluates effects on overall survival (OS) and EOL healthcare use. Methods: We abstracted dates of death, emergency department (ED), hospitalization, palliative care (PC), and hospice use within and outside Veterans Affairs (VA) using electronic health record and claims before data cut-off on February 1, 2023 for all EPAC participants. We compared OS using Kaplan Meier and log-rank, risk of death using Cox-proportional hazard models, ED, hospitalization, PC, and hospice use in the last 30 days of life using Logistic Regression, and incidence rate ratios of ED and hospitalizations using Poisson regression. Results: Among 213 participants, there were no imbalances in demographic or clinical characteristics. 165 (77.4%) were White, 211 (99%) males, 80 (37.6%) had lung cancer, and 118 (55.3%) had stage 4 disease. Median follow-up was 298 days (range 12-3438). Intervention group participants had greater OS (log rank p=0.04), 25% reduction in risk of death, lower acute care use, and greater PC and hospice use than control group participants. Conclusions: The CHW-led intervention significantly improved OS and maintained robust effects on EOL healthcare use. The intervention may have had unintended, unmeasured effects on other aspects of care, such as treatment and follow-up adherence, and/or hospice acceptance, which require investigation. Nonetheless, results support integration of community health workers into cancer care to improve clinical outcomes. Clinical trial information: NCT02966509 .[Table: see text]
The practice of thyroid monitoring in patients treated with lenalidomide for hematological malignancies: A single-center retrospective analysis.
Authors: rachaita lakra, Zara Hassan, Poornima Ramadas
Journal: Journal of Clinical Oncology (2023)

e14535 Background: Thyroid dysfunction in the form of both hypothyroidism and hyperthyroidism is a known fact and is seen in 5-10 % of patients treated with Lenalidomide. Since the potential impact of thyroid disease on a patient being treated for malignancies can be devastating, surveillance evaluation of thyroid function has been recommended on a bi-monthly basis. This single center retrospective analysis is an effort to understand if this recommendation is practiced by hematologists. Methods: Data for this retrospective chart review was extracted from electronic medical records. 225 patients who received Lenalidomide from the year January 2019 to October 2022 were included. Thyroid monitoring was estimated through thyroid stimulating hormone (TSH) if done and was further classified as baseline (TSH before lenalidomide initiation) versus three months. Abnormal thyroid testing was perceived as TSH outside of our institute’s normal range (0.40-4.0 uIU/mL). Any other risk factors of developing thyroid disease (neck radiation exposure, autoimmune disorders or other drugs contributing to thyroid disfunction) were also recorded. Descriptive statistics with interquartile ranges and frequencies were analyzed. Results: Doses of Lenalidomide used ranged between 5 and 25 mg, over a time period ranging between 1 and 48 months. Reasons for discontinuation of Lenalidomide included bone marrow suppression (N=32, 14%), neuropathy (N=14, 0.06%), intolerable fatigue (N=7, 0.03%) and one patient had concerns for drug induced hypothyroidism. Seven patients were found to have pre-existing thyroid disease, which was well controlled with replacement before initiation of Lenalidomide. 52% had a baseline TSH documented prior to initiation of treatment, while only 18 patients (0.08%), had three monthly thyroid monitoring. Conclusions: Lenalidomide caused hypothyroidism was seen in one of our patients, however 48% never had a TSH documented, while 99.2% were not monitored as per recommendations. This study reflects on the principle of “primum non nocere” and adequate treatment of missed thyroid anomalies in patients treated with lenalidomide can improve quality of life. We recommend hard reminders of bi-monthly TSH monitoring through electronic medical record, for patients receiving Lenalidomide which has been initiated in our institute post this study.
Retrospective cohort study of CDK4/6-inhibitor-induced alopecia in patients with breast cancer.
Authors: Abena Minta, Lucy Rose, Candice Park, Stephanie Trovato, Maryam B. Lustberg, Preeti Khetarpal Sudheendra, Mathew Amprayil Cherian, Margaret Elena Gatti-Mays, Daniel G. Stover, Robert Wesolowski, Sagar D. Sardesai, Bhuvaneswari Ramaswamy, Nicole Olivia Williams, Brittany Dulmage
Journal: Journal of Clinical Oncology (2023)

e13083 Background: The synergistic effects of novel combined cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) and endocrine therapy has increased their utilization for treatment of metastatic breast cancer. When compared to endocrine monotherapy, CDK4/6i may increase the risk of alopecia by nearly two-fold (Eiger D, et al. PMID: 32167397; Chan D, et al. J Clin Oncol.). The prevalence of this adverse effect underscores the importance of characterizing CDK4/6i-induced alopecia (CDKIA) and investigating therapeutic options. Methods: A retrospective cohort of 28 female patients with breast cancer and endocrine-induced alopecia (EIA) or CDKIA. Onset of alopecia was measured by time (months) between initiation of anticancer therapy and dermatology referral. Therapeutic response to minoxidil (LDOM or topical [5%] solution or foam) was assessed by both Dean Scale and qualitative clinical improvement by comparison of pre-treatment and post-treatment clinical images by 2 board certified academic dermatologists (ST and BD). Results: Androgenetic alopecia was the most common hair loss distribution (n=27, 96.4%), with CDKIA patients having preferential vertex involvement (n=7 [70.0%] CDKIA vs. n=4 [36.4%] EIA; p=0.04). Patients on CDK4/6i had shorter times to dermatology referral (mean time [months]: 44.6±37.1 for EIA vs. 9.4±13.7 CDKIA; p=0.003). After 16-24 weeks of minoxidil, moderate to significant improvement of alopecia occurred in 80% of CDKIA patients versus 94.4% of EIA patients. Despite similar baseline alopecia grade severity, significant improvement was only observed in EIA patients (mean pretreatment Dean Score – post-treatment Dean Score: -0.44; p=0.0002). Conclusions: Compared to EIA, the onset of CDKIA happened more rapidly and was more resistant to minoxidil. The preferential vertex involvement observed among patients with CDKIA may suggest combination therapy with topical or oral minoxidil and topical anti-androgens may lead to more favorable outcomes. Prompt dermatology referral should be considered for patients treated with CDK4/6i + ET. [Table: see text]
De novo metastatic Her2+ breast cancer in a diverse population of women under age 40.
Authors: Victoria Chung, Melanie Anne Sheen, Marcia Henry, Matthew Alberti, James Peeples, Helen Yuan, Raina Saxena, Susan Olet, Caitlin Taylor, Rabia Cattie
Journal: Journal of Clinical Oncology (2023)

e13045 Background: Breast cancer (BC) is the most common malignancy among women. Her2 mutation has historically been associated with more aggressive disease and worse prognosis, however this paradigm is changing with Her2-directed therapies. Her2 positive BC presents with de novo metastatic disease more often than other subtypes. Young women are more likely to be diagnosed with Her2 positive BC, however previous studies have not had adequate representation of Black/African American women. We evaluated a diverse group of young women under the age of 40 to determine if Her2+ disease was more likely to present with de novo metastatic disease. Methods: We performed a retrospective chart review and collected data on 746 women diagnosed with BC under the age of 40 from 2012 to 2022. We collected age at diagnosis, Her2 receptor status, self-identified race, and stage at diagnosis. 187 of these patients were Her2 positive, and 276 patients were Black. We stratified patients as Black versus White, and as stage IV at diagnosis versus stages I to III at diagnosis. We performed Fisher's exact test to determine if Her2 positive BC was more or less likely to present as de novo metastatic disease compared to Her2 negative BC. Results: In our population of 746 young women under the age of 40 presenting to our health system in a 10-year period, 48 (6.4%) presented with de novo metastatic BC, and 19 (39.6%) of these were Her2 positive. 36% of our study population was Black, which is representative of the demographics of our region. We performed Fisher's exact test, and found that Her2 positive BC was more likely to present as de novo metastatic disease compared to Her2 negative BC. This was statistically significant (p = 0.024). When divided for race, this was not statistically significant for White patients alone (p = 0.052) or Black patients alone (p = 0.234). Conclusions: Our data shows that Her2 positive BC in women under the age of 40 is statistically more likely to present with de novo metastatic disease. Previous research in this area has not been inclusive of Black patients. Current guidelines only recommend staging imaging among patients with systemic symptoms. Based on this data, consideration should be made for staging scans for young women presenting with new HER2+ breast cancer diagnoses. There is limited data available for breast cancer subtype incidence and prognosis among Black patients, and this study underscores the need for more inclusive study populations.[Table: see text]
Childhood leukemia survival in the US-Mexico border: Building sustainable leukemia care using health systems strengthening models.
Authors: Paula Aristizabal, Rebeca Rivera Gomez, Raul Correa Ribeiro, William Roberts
Journal: Journal of Clinical Oncology (2023)

1502 Background: Pediatric leukemia outcomes are poor in most low-and middle-income countries (LMIC) and exacerbated by healthcare systems ill-equipped to manage cancer. Effective leukemia management in LMIC involves curating epidemiologic data; providing healthcare workforce specialty training; developing evidence-based treatments and supportive care; safeguarding access to medications and equipment; providing patient and family psychosocial and financial support; partnering with non-governmental organizations, and ensuring treatment adherence. Methods: We describe the implementation of a collaborative program to achieve sustainable high-quality care for children with leukemia in a unique border health setting. In 2013, in a partnership between North-American and Mexican institutions, we used the health systems strengthening model developed by the World Health Organization (WHO) Framework for Action with domains in Services delivery, Workforce, Information systems, Access to essential medicines, Financing, and Leadership and Governance to implement a sustainable program aimed at improving acute lymphoblastic leukemia (ALL) outcomes at a public, referral hospital in the US-Mexico border region. We evaluated program sustainability indicators, and prospectively assessed clinical features, risk classification, and survival outcomes in children with ALL at Hospital General in Tijuana, Mexico from 2008-2012 (pre-implementation) and from 2013-2017 (post-implementation). Results: Our approach led to a fully-staffed leukemia service, sustainable training programs, evidence-based, data-driven projects to improve clinical outcomes, and funding for medications, supplies and personnel through local partnerships. Pre-implementation and post-implementation 5-year overall survival for children with standard-risk and high-risk ALL improved from 52% to 82% (P = 0 ×023) and from 46% to 76% ( P = 0 ×031), respectively. All sustainability indicators significantly improved between 2013 and 2017. Conclusions: By using a health systems strengthening approach, we improved leukemia care and survival in a public Mexican hospital in the US-Mexico border region. The demonstrated increase in overall survival across a decade after the implementation of our program validates the use of the health systems strengthening models, as they are not only efficacious in improving clinical outcomes, but also serve as financially and organizationally means of building sustainable capacity. Our model serves as an example for future international partnerships aimed at sustainably improving cancer outcomes in LMIC. Future research should evaluate best practices in establishing global health collaborations with particular attention paid towards the individual circumstances that impact healthcare delivery locally in each unique community.